CRCNS: Cholinergic contribution to hippocampal information processing

CRCNS：胆碱能对海马信息处理的贡献

• 批准号: 10183326
• 负责人: Carmen Castro Canavier
• 金额: $ 36.5万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10183326
• 关键词: Acetylcholine; Affect; Area; Attenuated; Behavior; Buffers; Cations; Cells; Code; Cognition Disorders; Cognitive Therapy; Complex; Computer Models; Data; Diffuse; Dose; Electrophysiology (science); Environment; Fire - disasters; Frequencies; Hippocampus (Brain); Image; Individual; Ion Channel; Lead; Learning; Location; Mediating; Memory; Mental disorders; Modeling; Myoepithelial cell; Neuromodulator; Neurons; Parvalbumins; Pattern; Pharmacology; Phase; Physiologic pulse; Play; Positioning Attribute; Process; Property; Pyramidal Cells; Ramp; Rattus; Recording of previous events; Retrieval; Role; Route; Sensory; Shapes; Slice; Stream; Structure; Synapses; Synaptic plasticity; Testing; Therapeutic; Visit; Work; attenuation; base; cholinergic; entorhinal cortex; experimental study; hippocampal pyramidal neuron; improved; in vivo; information processing; model development; neurotransmitter release; optogenetics; patch clamp; place fields; predictive modeling; prospective; relating to nervous system; response; two-photon

Area CA 1 of the hippocampus plays a key role in learning and memory. CA 1 pyramidal neurons receive two major input streams, one from the entorhinal cortex that mediates sensory information about the external world, and another from area CA3 that mediates retrieval of previously stored representations. The neuromodulator acetylcholine (ACh) is thought to gate encoding and retrieval. Our preliminary results indicate that ACh, by activating the Ca2+-activated nonspecific cation current ICAN and modulating other ion channels, dramatically affects the intrinsic response to a triangular current ramp simulating the excitatory input, thus levels of ACh may regulate the pattern of place field firing by shifting the peak to later positions in ramp. This shift could cause the coding to shift from prospective, representing upcoming locations, to retrospective, representing recently visited locations, which may favor encoding over retrieval. Our preliminary data also shows that ACh can induce sustained firing; since novelty increases ACh levels, this persistent firing may facilitate the synaptic plasticity required to form new place fields. Moreover, we find that there are both intrinsic and synaptic mechanisms that endow CA 1 pyramidal neurons with low pass filtering capabilities specific to the Schaffer collateral (SC) inputs from CA3, and that these capabilities are switched off by ACh. In Aim 1, we test the hypothesis that cholinergic modulation converts the shape of the rate response to a triangular current ramp from decelerating to accelerating in a dose-dependent fashion, with a concomitant shift in the peak. In Aim 2, we test the hypotheses that intrinsic properties of CA 1 neurons mediate low pass filtering of SC inputs, with a critical additional component provided by parvalbumin-positive (PV+) basket cells, and that cholinergic modulation removes the low pass filtering, such that CA 1 can follow higher input frequencies from CA3. This work seeks to elucidate the neural bases of complex behaviors and mental illnesses. Better understanding of the mechanisms underlying cholinergic modulation of neuronal ensembles may lead not only to an improved understanding of information processing important in learning and memory, but eventually to improved therapies for cognitive disorders.

海马的区域Ca 1在学习和记忆中起关键作用。 Ca 1锥体神经元接受两个 主要输入流，其中一流来自内河皮层，介导了有关外部的感官信息 世界，另一个来自CA3区域的介导了以前存储的表示的检索。这 神经调节剂乙酰胆碱（ACH）被认为是栅极编码和检索。我们的初步结果 通过激活Ca2+激活的非特异性阳离子电流ICAN并调节其他 离子通道极大地影响对模拟兴奋性的三角电流坡道的内在响应 输入，因此ACH的水平可以通过将峰转移到以后的位置来调节位置场射击的模式 坡道。这种转变可能会导致编码从代表即将到来的位置的潜在的转变到 回顾性，代表最近访问的地点，这可能有利于编码而不是检索。我们的 初步数据还表明，ACH可以诱导持续的射击。由于新颖性提高了ACH水平，因此 持续的射击可能有助于形成新地方场所需的突触可塑性。而且，我们发现 既有内在的和突触机制 CA3的Schaffer抵押品（SC）输入的功能，这些功能已切换 由ACH离开。在AIM 1中，我们检验了胆碱能调节的假设转化了速率的形状 以剂量依赖性的方式对三角电流的反应，以 峰值伴随移动。在AIM 2中，我们检验了Ca 1神经元的内在特性的假设 介导SC输入的低通滤波，并具有关键的其他组件由白蛋白阳性阳性 （PV+）篮细胞，并且该胆碱能调节消除了低通滤波，因此Ca 1可以跟随 CA3的较高输入频率。这项工作旨在阐明复杂行为的神经基础和 精神疾病。更好地了解神经元胆碱能调节的机制 合奏不仅可能导致对信息处理至关重要的信息处理的理解 和记忆，但最终改善了认知障碍的疗法。

项目成果

Phase response theory explains cluster formation in sparsely but strongly connected inhibitory neural networks and effects of jitter due to sparse connectivity.

相位响应理论解释了稀疏但强连接的抑制神经网络中的簇形成以及稀疏连接引起的抖动影响。

• DOI: 10.1152/jn.00728.2018
• 发表时间: 2019
• 期刊: Journal of neurophysiology
• 影响因子: 2.5
• 作者: Tikidji-Hamburyan,RubenA;Leonik,ConradA;Canavier,CarmenC
• 通讯作者: Canavier,CarmenC

Shunting Inhibition Improves Synchronization in Heterogeneous Inhibitory Interneuronal Networks with Type 1 Excitability Whereas Hyperpolarizing Inhibition Is Better for Type 2 Excitability.

分流抑制可改善具有 1 型兴奋性的异质抑制性中间神经元网络的同步性，而超极化抑制则更适合 2 型兴奋性。

• DOI: 10.1523/eneuro.0464-19.2020
• 发表时间: 2020
• 期刊: eNeuro
• 影响因子: 3.4
• 作者: Tikidji-Hamburyan,RubenA;Canavier,CarmenC
• 通讯作者: Canavier,CarmenC

Long-Term Inactivation of Sodium Channels as a Mechanism of Adaptation in CA1 Pyramidal Neurons.

钠通道的长期失活作为 CA1 锥体神经元的适应机制。

• DOI: 10.1523/jneurosci.1914-21.2022
• 发表时间: 2022
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Upchurch,CarolM;Combe,CrescentL;Knowlton,ChristopherJ;Rousseau,ValeryG;Gasparini,Sonia;Canavier,CarmenC
• 通讯作者: Canavier,CarmenC